BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors

NCT01297452 | Completed Phase 1 DMC

• 1 other identifier: 10-192
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out the good and bad effects that occur when BKM120 is added to standard chemotherapy with carboplatin and paclitaxel.

Conditions

Solid Tumors

Keywords

BKM120; CARBOPLATIN; TAXOL (PACLITAXEL); Chemotherapy; 10-192

Outcome Measures

Primary Outcomes (3)

• To establish the phase II recommended dose of daily oral BKM120

  for patients with advanced solid tumors, BKM120 in combination with two different schedules of paclitaxel and carboplatin.

  2 years

• EXPANSION COHORT A:To evaluate the safety and tolerability of daily oral BKM120 (100 mg) + paclitaxel (200 mg/m2) + carboplatin (AUC 6), both given intravenously (IV) on day 1 of a 21-day cycle, with pegfilgrastim support

  2 years

• EXPANSION COHORT B: To obtain a preliminary description of efficacy of the regimen established in Group 1 among patients with tumors harboring PTEN mutation or homozygous deletion.

  2 years

Secondary Outcomes (4)

• To describe the safety of BKM120 combined with paclitaxel and carboplatin,

  weekly clinic visits during Cycle 1, on Day 1 of subsequent cycles,

• To determine the pharmacokinetic profile of daily BKM120.

  2 years

• To describe and tabulate the radiographic response rate of BKM120 in combination with carboplatin and paclitaxel,

  2 years

• Correlative Tissue Studies

  2 years

Study Arms (4)

BKM120 (days 1 - 21) + paclitaxel + carboplatin

EXPERIMENTAL

This will be a single institution phase I study. The primary objectives are to determine the maximum tolerated dose of BKM120 administered with paclitaxel + carboplatin on both a 21-day cycle with growth factor support (Group 1)

Drug: BKM120 days 1 - 21 plus paclitaxel + carboplatin; Drug: BKM120, Paclitaxel + Carboplatin

BKM120 (days 1 - 28, ) + paclitaxel + carboplatin

EXPERIMENTAL

This will be a single institution phase I study. The primary objectives are to determine the maximum tolerated dose of BKM120 administered + paclitaxel with carboplatin on a 28-day cycle with growth factor support and a 28-day cycle (Group 2).

Drug: BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin

BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)

EXPERIMENTAL

EXPANSION COHORT A BKM120 100 mg (days 1 - 21, per dose escalation scheme) plus paclitaxel (200 mg/m2 intravenously, day 1) + carboplatin (AUC 6 intravenously, day 1) on a 21-day cycle. After enrollment to Groups 1 and 2 has been completed and all patients in Group 1 and 2 have completed the DLT monitoring period, up to 6 additional patients will be enrolled in this EXPANSION COHORT A.

Drug: BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)

BKM120 (days 1 - 21) + paclitaxel + carboplatin exp B

EXPERIMENTAL

Expansion Cohort B will be restricted to patients with tumors known to harbor PTEN mutation or homozygous deletion. The regimen in Expansion Cohort B will be the same regimen established in Group 1 of the protocol, with BKM120 (now called buparlisib) at 100 mg/day per oral + paclitaxel (175 mg/m2) + carboplatin (AUC 5), both given intravenously (IV) on day 1 of a 21-day cycle

Drug: BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin

Interventions

BKM120 days 1 - 21 plus paclitaxel + carboplatin DRUG

Patients will receive oral daily BKM120 (days 1 - 21, per dose escalation scheme) plus paclitaxel (175 mg/m2 intravenously, day 1) + carboplatin (AUC 5 intravenously, day 1)on a 21-day cycle. Pegfilgrastim (6 mg/subcutaneously) will be administered on day 2 of each cycle.

BKM120 (days 1 - 21) + paclitaxel + carboplatin

BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin DRUG

Patients will receive oral daily BKM120 (days 1 - 28, per dose escalation scheme) plus paclitaxel (80 mg/m2 intravenously, days 1, 8 and 15) + carboplatin (AUC 5 intravenously, day 1) on a 28-day cycle.

BKM120 (days 1 - 21) + paclitaxel + carboplatin exp B; BKM120 (days 1 - 28, ) + paclitaxel + carboplatin

BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1) DRUG

BKM120 100 mg (days 1 - 21, per dose escalation scheme) plus paclitaxel (200 mg/m2 intravenously, day 1) + carboplatin (AUC 6 intravenously, day 1) on a 21-day cycle. After enrollment to Groups 1 and 2 has been completed and all patients in Group 1 and 2 have completed the DLT monitoring period, up to 6 additional patients will be enrolled in this EXPANSION COHORT.A

BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)

BKM120, Paclitaxel + Carboplatin DRUG

BKM120 100 mg per oral, days 1 - 21 Paclitaxel (175 mg/m2) intravenously on Day 1 Carboplatin (AUC 5) intravenously on Day 1 EXPANSION COHORT B

BKM120 (days 1 - 21) + paclitaxel + carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed recurrent or metastatic advanced solid tumor, for which there is no curative-intent treatment option. Pathology confirmation must be performed at MSKCC.
• Age ≥ 18 years
• ECOG performance status ≤ 1
• Life expectancy of ≥ 12 weeks
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin \> 9 g/dL
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium ≥ the lower limit of normal
• Adequate liver function.
• Serum bilirubin must be within the upper limit of normal. (ULN). AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used.
• Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 55 mL/min
• Fasting plasma glucose (FPG) ≤120 mg/dL or ≤6.7 mmol/L
• HbA1c ≤ 8%
• Negative serum pregnancy test within 14 days before starting study treatment in women with childbearing potential
• Ability to swallow oral medication
• EXPANSION COHORT B ONLY: Documented genetic alteration (mutation or homozygous deletion) in the PTEN gene, identified by the MSKCC IMPACT assay platform or other CLIA-approved test.

You may not qualify if:

• Patients who have received prior treatment with a P13K inhibitor.
• Patients with a known hypersensitivity to BKM120 or to its excipients
• Patients with untreated brain metastases are excluded. However, patients with metastatic CNS tumors may participate in this trial, if the patient is \> 4 weeks from therapy completion (incl. radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:
• medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
• \*≥ CTCAE grade 3 anxiety
• At screening, mood rating scores of ≥ 10 on PHQ-9 and/or ≥ 15 on GAD-7, unless overruled by psychiatrist's assessment
• Patient selects a response of "1, 2, or 3" for question 9 on PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9) Note: The psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment. If mood rating scores do not meet eligibility criteria and/or the investigator deems that a patient has mood disorder that renders the patient ineligible, that patient may not be registered to the study unless there is a subsequent psychiatric clinic consultation in which the psychiatrist overrules the mood assessment questionnaire result/investigator judgment.
• Patients with diarrhea ≥ CTCAE grade 2
• Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• ST depression or elevation of ≥ 1.5 mm in 2 or more leads
• Congenital long QT syndrome
• History or presence of sustained ventricular arrhythmias or atrial fibrillation
• Clinically significant resting bradycardia (\< 50 beats per minutes) QTc \> 480 msec on screening ECG

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator
• Sai Life Sciences: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (2)

• Smyth LM, Monson KR, Jhaveri K, Drilon A, Li BT, Abida W, Iyer G, Gerecitano JF, Gounder M, Harding JJ, Voss MH, Makker V, Ho AL, Razavi P, Iasonos A, Bialer P, Lacouture ME, Teitcher JB, Erinjeri JP, Katabi N, Fury MG, Hyman DM. A phase 1b dose expansion study of the pan-class I PI3K inhibitor buparlisib (BKM120) plus carboplatin and paclitaxel in PTEN deficient tumors and with dose intensified carboplatin and paclitaxel. Invest New Drugs. 2017 Dec;35(6):742-750. doi: 10.1007/s10637-017-0445-0. Epub 2017 Mar 9.

  PMID: 28281183 DERIVED

• Hyman DM, Snyder AE, Carvajal RD, Gerecitano JF, Voss MH, Ho AL, Konner J, Winkelmann JL, Stasi MA, Monson KR, Iasonos A, Spriggs DR, Bialer P, Lacouture ME, Teitcher JB, Katabi N, Fury MG. Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors. Cancer Chemother Pharmacol. 2015 Apr;75(4):747-55. doi: 10.1007/s00280-015-2693-z. Epub 2015 Feb 12.

  PMID: 25672916 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Paclitaxel; Carboplatin; NVP-BKM120

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• David Hyman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2011
• First Posted: February 16, 2011
• Study Start: February 15, 2011
• Primary Completion: March 29, 2017
• Study Completion: March 29, 2017
• Last Updated: March 31, 2017

Record last verified: 2017-03

Locations

US (1)